High blood pressure and stroke afflict 10-30% of the adult population in this country. The mechanisms of cardiovascular complications in these conditions are not clearly understood. In order to unravel these mechanisms, it is necessary to know how different "neuronal pools" in the central nervous system regulate cardiovascular function normally. Information available on these mechanisms is incomplete. The long-term goal of this grant application is to gain a better understanding of the central regulation of cardiovascular function. Eventually the information generated from these investigations is likely to be useful in the treatment of cardiovascular disorders such as hypertension and stroke. During the previous funding periods, cardiovascular reflex mechanisms were studied in normotensive and hypertensive animals. This was followed by the functional identification of the pathways and neurotransmitters involved in these reflexes. Cardiovascular pressor and depressor areas in the brainstem and sympathoexcitatory areas in athe spinal cord were then identified in normotensive animals. In the present proposal, which is a logical extension of previous studies, functional relationship between different brainstem cardiovascular areas, their interaction with intermediolateral cell column of the thoraco-lumbar spinal cord and identification of putative neurotransmitters in the pathways interconnecting these cardiovascular regulatory mechanisms will be investigated. There are several gaps in our knowledge on this topic. These issues will be addressed in the following specific aims: 1) Identification of the neurotransmitters and pathways mediating carotid chemoreceptor reflex in the ventrolateral medulla and the spinal cord. 2) Investigation of the modulatory role of alpha adrenergic receptors at the target sites of the projection from rostral ventrolateral medulla to the spinal cord. 30 Functional identification of other cell groups (e.g. A5 noradrenergic cells) in the brainstem sending projections to the intermediolateral cell column in which norepinephrine may be the modulator.